In natural infections of humans with oncogenic viruses like the Epstein-Barr virus and human T cell leukemia virus, it is thought that virus dormancy in lymphoid tissues is both the cause and the consequence of persistent immunity. Latently infected cells may proliferate or reactivate oncogenic viruses when freed from host immunosurveillance by culture in vitro or immunomodulation in vivo. Recently, in vitro culture techniques have established that latent/reactivatable virus detentes are common in the bone marrow and lymph nodes of healthy cats immune to the feline leukemia virus (FeLV). Immunosuppression of immune cats with high doses of corticosteroids leads to the in vivo recrudescence of FeLV and viremia. That FeLV also can be reactivated from the marrow of pet cats with FeLV-negative leukemias strongly suggests the direct involvement of FeLV in nonproducer lymphomagenesis. In viremic cats, the disappearance of FeLV from preleukemic T cells and its reappearance in leukemic T cells implicate latent FeLV infections in producer lymphomagenesis. The objective of this proposal is to characterize the role of silent, reactivatable, feline retroviruses in nonproducer and producer lymphomagenesis. Specific aims are to determine how serum factors, autoregulatory lymphoid subsets and virus receptors control FeLV replication in lymphocyte and marrow cultures established from uninfected, latently infected, and acutely infected cats. Other experiments will test the lymphomagenicity of the novel retroviruses reactivated from leukemic and healthy cat marrows in susceptible neonates. A major aim is to develop an animal model for retrovirus-induced, nonproducer lymphoma. One approach will be to determine if lymphocytes latently infected with FeLV in vitro became leukemic when inoculated into autochthonous recipients in vivo. The other approach will determine if immunostimulation (Protein A) or immunoabrogation (low dose corticosteroids, cyclosporin A) will facilitate the escape of nonproducer lymphoma cells in immune cats in vivo. Information provided by the latent FeLV model should be relevant to the biology of virus-negative and -positive tumors in man.